The overall objectives of the total project are to elucidate the mechanism of action of insecticides on the nerve membrane which is the most critical target site of a variety of insecticides. In particular the interactions of insecticides such as DDT, cyclodienes, pyrethroids and their analogs with nerve membrane ionic channels are analyzed by means of voltage clamp techniques. These studies will provide the basis of the molecular mechanism of action of insecticides. The structure-activity relationships of synthetic pyrethroids and DDT are also studied by comparison of the direct action on the nervous tissue. This analysis is expected to provide clear-cut answers since no other factors such as cuticle penetration and detoxication inherent to the conventional measurements of insecticidal potency are involved. The results of the proposed project will have a significant impact on the improvement of insecticides and the development of therapeutics for insecticide intoxication. BIBLIOGRAPHIC REFERENCES: Wang, C.M>, T. Narahashi and J. Fukami (1975). Mechanism of neuromuscular block by chlordimeforem. Pesticide Biochem. Physiol. 5, 11-125. Wu, C.H., J. van den Bercken and T. Narahashi (1975). The structure-activity relationship of DDT analogs in crayfish giant axons. Pesticide Biochem. Physiol. 5, 142-149.